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Physostigmine: Drug information

Physostigmine: Drug information
(For additional information see "Physostigmine: Pediatric drug information" and see "Physostigmine: Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Pharmacologic Category
  • Acetylcholinesterase Inhibitor;
  • Antidote
Dosing: Adult

Note: Consultation with a clinical toxicologist or poison control center is recommended prior to use.

Reversal of toxic anticholinergic effects

Reversal of toxic anticholinergic effects: Note: When administering by IV injection, administer no more rapidly than 1 mg/minute to prevent bradycardia, respiratory distress, and seizures from too rapid administration. Slower administration (ie, over ≥5 minutes) may be preferable. The duration of action of some anticholinergic agents may exceed the duration of action of physostigmine; therefore, monitor closely for recurrence of symptoms (Ref).

IM, IV: Initial: 0.5 to 2 mg; may repeat every 10 to 30 minutes until response occurs. Generally, a single dose or a short duration of treatment (<6.5 hours) is sufficient (Ref); longer durations of therapy may be required to manage life-threatening anticholinergic effects (Ref).

Dosing: Kidney Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling.

Dosing: Hepatic Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling.

Dosing: Older Adult

Refer to adult dosing.

Dosing: Pediatric

(For additional information see "Physostigmine: Pediatric drug information")

Reversal of toxic anticholinergic effects

Reversal of toxic anticholinergic effects:

Note: Reserve for life-threatening situations only. Slow IV administration (≤0.5 mg/minute for pediatric patients) is required to prevent bradycardia, respiratory distress, and seizures. Slower administration (ie, over no less than 5 minutes) may be preferable (Ref). The duration of action of some anticholinergic agents may exceed the duration of action of physostigmine; therefore, monitor closely for recurrence of symptoms (Ref). Consultation with a clinical toxicologist or poison control center is recommended.

Infants, Children, and Adolescents: IM, IV: Initial: 0.02 mg/kg; maximum dose: 0.5 mg/dose; may repeat every 5 to 15 minutes until response occurs (Ref); maximum total dose: 2 mg (total). Subsequent doses may be required to manage clinical relapse (Ref). Based on adult experience, a short total duration of therapy (<6.5 hours) is often adequate (Ref). Higher cumulative doses or prolonged therapy may be necessary in some cases; in one case report, an 11-year-old initially responded to 1.5 mg of physostigmine for antimuscarinic delirium and agitation with a good response. As the physostigmine effects diminished, agitation returned, which was unresponsive to benzodiazepines and required 4 additional 1 mg doses of physostigmine administered over 6 hours (Ref).

Dosing: Kidney Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling.

Dosing: Hepatic Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling.

Adverse Reactions (Significant): Considerations

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

Frequency not defined:

Cardiovascular: Bradycardia

Gastrointestinal: Nausea, salivation, vomiting

Nervous system: Seizures

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

Frequency not defined:

Cardiovascular: Bradycardia

Gastrointestinal: Nausea, salivation, vomiting

Nervous system: Seizures

Contraindications

Gastrointestinal or genitourinary obstruction; asthma; gangrene; diabetes; cardiovascular disease; any vagotonic state; coadministration of choline esters and depolarizing neuromuscular-blocking agents (eg, succinylcholine).

Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Note: Physostigmine should not be used in the absence of toxicity from an anticholinergic agent (Howland 2019).

Warnings/Precautions

Concerns related to adverse effects:

• Arrhythmias: Patient should have a normal QRS interval, as measured by ECG, in order to receive physostigmine; use caution in poisoning with agents known to prolong intraventricular conduction (Arens 2019).

• Cholinergic effects: Symptoms of excessive cholinergic activity may occur (eg, salivation, urinary incontinence, defecation, vomiting). If excessive diaphoresis or nausea occurs, reduce subsequent doses. Atropine should be available to reverse cholinergic symptoms, if necessary.

• Hypersensitivity reactions: Hypersensitivity reactions may occur in patients with allergy to cholinesterase inhibitors or salicylates.

• Seizure: Use with caution in patients with a known seizure disorder or coingestion of epileptogenic drugs. Risk of seizure activity increases with too rapid administration.

Dosage form specific issues:

• Benzyl alcohol and derivatives: Some dosage forms may contain benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP ["Inactive" 1997]; CDC 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol with caution in neonates. See manufacturer's labeling.

• Sodium metabisulfite: Products may contain sodium metabisulfite which may cause allergic reactions in some individuals.

Other warnings/precautions:

• IV administration: Administer no more rapidly than 1 mg/minute in adults or 0.5 mg/minute in children to prevent bradycardia, respiratory distress, and seizures from too rapid administration. Administration at an even slower rate (ie, over no less than 5 minutes) may be preferable (Howland 2019). Although the use of a continuous infusion of physostigmine has been described in the literature (Eyer 2008; Hail 2013; Phillips 2014; Wang 2021), the routine use of a continuous infusion is not recommended. A continuous infusion may be considered for patients with profound anticholinergic effects who require frequent doses of physostigmine. However, it is preferable to titrate physostigmine to patient needs through the use of intermittent administration.

• Tricyclic antidepressant (TCA) poisoning: Asystole and seizures have been reported when physostigmine was administered to TCA poisoned patients (Pentel 1980). Physostigmine is not recommended in patients with known or suspected TCA intoxication.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Solution, Injection, as salicylate:

Generic: 1 mg/mL (2 mL [DSC])

Generic Equivalent Available: US

Yes

Pricing: US

Solution (Physostigmine Salicylate Injection)

1 mg/mL (per mL): $46.97

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Administration: Adult

IV: Infuse no more rapidly than 1 mg/minute. Too rapid administration may cause bradycardia, respiratory distress, and seizures. Slower administration (ie, over ≥5 minutes) may be preferable (Ref). May also be administered IM (Ref).

Administration: Pediatric

Parenteral:

IM: May administer as undiluted solution.

IV: Infuse undiluted solution slowly; maximum rate: Pediatric patients: 0.5 mg/minute; a higher maximum rate in adults: 1 mg/minute. Slower administration (ie, over ≥5 minutes) may be preferable (Ref). Too rapid administration can cause bradycardia and hypersalivation leading to respiratory distress and seizures.

Hazardous Drugs Handling Considerations

Hazardous agent; use appropriate precautions for handling and disposal (EPA, P-listed).

Use: Labeled Indications

Reversal of central nervous system anticholinergic syndrome

Note: The decision to use physostigmine should be made in consultation with a clinical toxicologist or poison control center, and the patient-specific risk-benefit ratio should always be considered. Physostigmine is most efficacious for agitation and/or delirium resulting from drugs with predominant anticholinergic properties (eg, atropine, benztropine, scopolamine, dimenhydrinate, diphenhydramine, oxybutynin), some plants from the Solanaceae family (eg, Atropa belladonna [deadly nightshade], jimson weed [Datura spp]), but may also be beneficial for other medications with anticholinergic effects (eg, atypical antipsychotics, cyclobenzaprine, hydroxyzine) (Arens 2018; Boley 2019a; Boley 2019b; Cole 2012; Dawson 2022; Grenga 2018; Khan 2021; Mullins 2022; Rasimas 2014; Wang 2021; Watkins 2015; Weizberg 2006; Whitledge 2023).

Medication Safety Issues
Sound-alike/look-alike issues:

PHYSostigmine may be confused with Prostigmin, pyRIDostigmine

Metabolism/Transport Effects

None known.

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Amifampridine: Acetylcholinesterase Inhibitors may enhance the therapeutic effect of Amifampridine. Amifampridine side effects may also be increased. Amifampridine may enhance the therapeutic effect of Acetylcholinesterase Inhibitors. Acetylcholinesterase inhibitor side effects may also be increased. Risk C: Monitor therapy

Anticholinergic Agents: Acetylcholinesterase Inhibitors may diminish the therapeutic effect of Anticholinergic Agents. Anticholinergic Agents may diminish the therapeutic effect of Acetylcholinesterase Inhibitors. Risk C: Monitor therapy

Benoxinate: Acetylcholinesterase Inhibitors may enhance the therapeutic effect of Benoxinate. Specifically, the effects of benoxinate may be prolonged. Risk C: Monitor therapy

Beta-Blockers: Acetylcholinesterase Inhibitors may enhance the bradycardic effect of Beta-Blockers. Risk C: Monitor therapy

Chlorprothixene: Acetylcholinesterase Inhibitors may enhance the adverse/toxic effect of Chlorprothixene. Acetylcholinesterase Inhibitors may enhance the therapeutic effect of Chlorprothixene. Risk C: Monitor therapy

Cholinergic Agonists: Acetylcholinesterase Inhibitors may enhance the adverse/toxic effect of Cholinergic Agonists. Specifically, cholinergic effects may be enhanced or increased. Risk C: Monitor therapy

Corticosteroids (Systemic): May enhance the adverse/toxic effect of Acetylcholinesterase Inhibitors. Increased muscular weakness may occur. Risk C: Monitor therapy

Dipyridamole: May diminish the therapeutic effect of Acetylcholinesterase Inhibitors. Risk C: Monitor therapy

Neuromuscular-Blocking Agents (Nondepolarizing): Acetylcholinesterase Inhibitors may diminish the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing). Risk C: Monitor therapy

Succinylcholine: Acetylcholinesterase Inhibitors may enhance the neuromuscular-blocking effect of Succinylcholine. Risk C: Monitor therapy

Pregnancy Considerations

Limited outcome data following maternal use of physostigmine as an antidote following acute poisoning (Zelner 2015) or to reverse the effects of scopolamine administered during labor (Boehm 1997; Smiler 1973; Smith 1976) are available.

In general, medications used as antidotes should take into consideration the health and prognosis of the mother; antidotes should be administered to pregnant patients if there is a clear indication for use and should not be withheld because of fears of teratogenicity (Bailey 2003).

Breastfeeding Considerations

It is not known if physostigmine is present in breast milk.

According to the manufacturer, the decision to breastfeed during therapy should consider the risk of exposure to the infant and the benefits of treatment to the mother.

Monitoring Parameters

ECG, vital signs; consult individual institutional policies and procedures.

Note: The duration of action of some anticholinergic agents may exceed the duration of action of physostigmine; therefore, monitor closely for recurrence of symptoms (Blackstone 2020; Howland 2019; Whitledge 2022).

Mechanism of Action

Physostigmine is a carbamate which inhibits the enzyme acetylcholinesterase and prolongs the central and peripheral effects of acetylcholine

Pharmacokinetics (Adult Data Unless Noted)

Onset of action: Within 3 to 8 minutes

Duration: 45 to 60 minutes

Absorption: IM: Readily absorbed

Distribution: Widely distributed throughout the body; crosses blood-brain barrier readily and reverses both central and peripheral anticholinergic effects

Metabolism: Via hydrolysis by cholinesterases

Half-life elimination: 1 to 2 hours

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (AT) Austria: Anticholium;
  • (CZ) Czech Republic: Anticholium;
  • (DE) Germany: Anticholium;
  • (LT) Lithuania: Anticholium | Physostigmin;
  • (LV) Latvia: Physostigmin;
  • (NO) Norway: Anticholium | Anticholium life | Anticholium nordic prime | Anticholium specific | Anticholium unimedic;
  • (PR) Puerto Rico: Antilirium
  1. Ahlfors CE. Benzyl alcohol, kernicterus, and unbound bilirubin. J Pediatr. 2001;139(2):317-319. [PubMed 11487763]
  2. Arens AM, Kearney T. Adverse effects of physostigmine. J Med Toxicol. 2019;15(3):184-191. doi:10.1007/s13181-019-00697-z [PubMed 31414401]
  3. Arens AM, Shah K, Al-Abri S, Olson KR, Kearney T. Safety and effectiveness of physostigmine: a 10-year retrospective review. Clin Toxicol. 2018;56(2):101-107. doi:10.1080/15563650.2017.1342828 [PubMed 28703024]
  4. Bailey B, "Are There Teratogenic Risks Associated With Antidotes Used in the Acute Management of Poisoned Pregnant Women?" Birth Defects Res A Clin Mol Teratol, 2003, 67(2):133-40. [PubMed 12769509]
  5. Blackstone NG, Olson A, Ainapurapu B. Physostigmine in anticholinergic poisoning: an old antidote with resurgence. Cureus. 2020;12(11):e11739. doi:10.7759/cureus.11739 [PubMed 33403170]
  6. Boehm FH, Egilmez A, Smith BE. Physostigmine's effect on diminished fetal heart rate variability caused by scopolamine, meperidine and propiomazine. J Perinat Med. 1977;5(5):214-222. doi:10.1515/jpme.1977.5.5.214 [PubMed 22596]
  7. Boley SP, Olives TD, Bangh SA, Fahrner S, Cole JB. Physostigmine is superior to non-antidote therapy in the management of antimuscarinic delirium: a prospective study from a regional poison center. Clin Toxicol. 2019a;57(1):50-55. doi:10.1080/15563650.2018.1485154 [PubMed 29956570]
  8. Boley SP, Stellpflug SJ. A comparison of resource utilization in the management of anticholinergic delirium between physostigmine and nonantidote therapy. Ann Pharmacother. 2019b;53(10):1026-1032. doi:10.1177/1060028019846654 [PubMed 31023063]
  9. Burns MJ, Linden CH, Graudins A, et al, “A Comparison of Physostigmine and Benzodiazepines for the Treatment of Anticholinergic Poisoning,” Ann Emerg Med, 2000, 35(4):374-81. [PubMed 10736125]
  10. Centers for Disease Control (CDC). Neonatal deaths associated with use of benzyl alcohol—United States. MMWR Morb Mortal Wkly Rep. 1982;31(22):290-291. http://www.cdc.gov/mmwr/preview/mmwrhtml/00001109.htm [PubMed 6810084]
  11. Cole JB, Stellpflug SJ, Ellsworth H, Harris CR. Reversal of quetiapine-induced altered mental status with physostigmine: a case series. Am J Emerg Med. 2012;30(6):950-953. doi:10.1016/j.ajem.2011.05.015 [PubMed 21802878]
  12. Dart RC, Goldfrank LR, Erstad BL, et al. Expert consensus guidelines for stocking of antidotes in hospitals that provide emergency care. Ann Emerg Med. 2018;71(3):314-325.e1. doi:10.1016/j.annemergmed.2017.05.021 [PubMed 28669553]
  13. Dawson A. Physostigmine should be used more readily for antimuscarinic toxicity: PRO. Br J Clin Pharmacol. 2022;88(1):58-60. doi:10.1111/bcp.15120 [PubMed 34705298]
  14. Eyer F, Jetzinger E, Pfab R, et al, “Withdrawal from High-Dose Tranylcypromine,” Clin Toxicol (Phila), 2008, 46(3):261-3. [PubMed 18344110]
  15. Glatstein MM, Alabdulrazzaq F, Garcia-Bournissen F, Scolnik D. Use of physostigmine for hallucinogenic plant poisoning in a teenager: case report and review of the literature. Am J Ther. 2012;19(5):384-388. [PubMed 20861718]
  16. Grenga PN, Schult RF, Wiegand TJ. Physostigmine use in clozapine intoxication from adulterated heroin: an atypical toxidrome with an effective antidote. Toxicol Communications. 2018;2(1):53-55.
  17. Hail SL, Obafemi A, and Kleinschmidt KC, “Successful Management of Olanzapine-Induced Anticholinergic Agitation and Delirium With a Continuous Intravenous Infusion of Physostigmine in a Pediatric Patient,” Clin Toxicol (Phila), 2013, 51(3):162-6. [PubMed 23473460]
  18. Healthcare Environmental Resource Center (HERC). Pharmaceuticals—Hazardous Waste. http://www.hercenter.org/hazmat/pharma.cfm#listed. Published 2015. Accessed October 23, 2016.
  19. Howland MA. Antidotes in depth: physostigmine salicylate. In: Nelson LS, Howland MA, Lewin NA, Smith SW, Goldfrank LR, Hoffman RS, eds. Goldfrank's Toxicologic Emergencies. 11th ed. McGraw-Hill; 2019.
  20. "Inactive" ingredients in pharmaceutical products: update (subject review). American Academy of Pediatrics (AAP) Committee on Drugs. Pediatrics. 1997;99(2):268-278. [PubMed 9024461]
  21. Jenike MA, Albert MS, Heller H, et al, “Oral Physostigmine Treatment for Patients With Presenile and Senile Dementia of the Alzheimer's Type: A Double-Blind Placebo-Controlled Trial,” J Clin Psychiatry, 1990, 51(1):3-7.
  22. Khan A, Singh G, Jacob J. A rare presentation of anticholinergic toxicity in a young patient due to over-the-counter cold medicines. Cureus. 2021;13(3):e13919. doi:10.7759/cureus.13919 [PubMed 33880270]
  23. Krenzelok EP, “Aspects of Datura Poisoning and Treatment,” Clin Toxicol, 2010, 48(2):104-110. [PubMed 20229618]
  24. Mullins ME. Physostigmine should be used more readily for antimuscarinic toxicity: CON. Br J Clin Pharmacol. 2022;88(1):61-63. doi:10.1111/bcp.15121 [PubMed 34784063]
  25. O'Donnell SJ, Burkhart KK, Donovan JW, et al, “Safety of Physostigmine Use for Anticholinergic Toxicity,” J Toxicol Clin Toxicol, 2002, 40(5):684.
  26. Pentel P and Peterson CD, “Asystole Complicating Physostigmine Treatment of Tricyclic Antidepressant Overdose,” Ann Emerg Med, 1980, 9(11):588-90. [PubMed 7001962]
  27. Phillips MA, Acquisto NM, Gorodetsky RM, Wiegand TJ. Use of a physostigmine continuous infusion for the treatment of severe and recurrent antimuscarinic toxicity in a mixed drug overdose. J Med Toxicol. 2014;10(2):205-209. [PubMed 24798647]
  28. Physostigmine injection [prescribing information]. Lake Forest, IL: Akorn Inc; April 2018.
  29. Rasimas JJ, Sachdeva KK, Donovan JW. Revival of an antidote: bedside experience with physostigmine. J Amer Acad Emerg Psychiatr. 2014;12:5-24.
  30. Refer to manufacturer's labeling.
  31. Rosenbaum C, Bird SB. Timing and frequency of physostigmine redosing for antimuscarinic toxicity. J Med Toxicol. 2010;6(4):386-392. [PubMed 20405266]
  32. Shenoi RP, Timm N; Committee on Drugs; Committee on Pediatric Emergency Medicine. Drugs Used to Treat Pediatric Emergencies. Pediatrics. 2020;145(1):e20193450. [PubMed 31871244]
  33. Smiler BG, Bartholomew EG, Sivak BJ, Alexander GD, Brown EM. Physostigmine reversal of scopolamine delirium in obstetric patients. Am J Obstet Gynecol. 1973;116(3):326-329. doi:10.1016/s0002-9378(15)31288-6 [PubMed 4707533]
  34. Smith DB, Clark RB, Stephens SR, Sherman RL, Hyde ML. Physostigmine reversal of sedation in parturients. Anesth Analg. 1976;55(4):478-480. doi:10.1213/00000539-197607000-00005 [PubMed 7975]
  35. Thornton SL, Farnaes L, Minns A. Prolonged antimuscarinic delirium in a child due to benztropine exposure treated with multiple doses of physostigmine. Pediatr Emerg Care. 2016;32(4):243-245. doi:10.1097/PEC.0000000000000503 [PubMed 26383155]
  36. Wang GS, Baker K, Ng P, et al. A randomized trial comparing physostigmine vs lorazepam for treatment of antimuscarinic (anticholinergic) toxidrome. Clin Toxicol. 2021;59(8):698-704. doi:10.1080/15563650.2020.1854281 [PubMed 33295809]
  37. Watkins JW, Schwarz ES, Arroyo-Plasencia AM, Mullins ME; Toxicology Investigators Consortium investigators. The use of physostigmine by toxicologists in anticholinergic toxicity. J Med Toxicol. 2015;11(2):179-184. doi:10.1007/s13181-014-0452-x. [PubMed 25510306]
  38. Weizberg M, Su M, Mazzola JL, Bird SB, Brush DE, Boyer EW. Altered mental status from olanzapine overdose treated with physostigmine. Clin Toxicol (Phila). 2006;44(3):319-325. doi:10.1080/15563650600584535. [PubMed 16749552]
  39. Whitledge JD, Watson CJ, Simpson M, et al. Diphenhydramine-induced antimuscarinic delirium treated with physostigmine and transdermal rivastigmine. J Med Toxicol. 2023;19(2):219-223. doi:10.1007/s13181-022-00925-z. [PubMed 36575250]
  40. Zelner I, Matlow J, Hutson JR, et al; Toxicology Investigators Consortium (ToxIC). Acute poisoning during pregnancy: observations from the Toxicology Investigators Consortium. J Med Toxicol. 2015;11(3):301-308. doi:10.1007/s13181-015-0467-y [PubMed 25783189]
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